Unexpected intruder: A rare case of mediastinal synovial sarcoma

Synovial sarcoma is a malignant mesenchymal tumor characterized by variable epithelial differentiation. It commonly arises in deep soft tissues of extremities particularly among adolescents and young adults [1]. Primary involvement of mediastinum is exceedingly rare, with only sporadic cases documented in the global literature [2]. When arising in mediastinum, synovial sarcoma poses a significant challenge due to its potential for local invasion and distant metastasis. Given its neoplastic clinical features and overlapping radiological features with other mediastinal masses, histopathological examination is essential for definitive diagnosis. We describe this case of a 10 cm primary mediastinal synovial sarcoma found in a 37-year-old male patient emphasizing the diagnostic conundrum associated with rare presentation.

A 37-year-old male exhibited symptoms of retrosternal chest pain, unrelated to physical activity or effort. He additionally reported dyspnea upon effort. There was an absence of cough, hemoptysis, fever, or weight loss in the medical history. No prior interaction with an active tuberculosis case. The physical examination was unremarkable and his initial laboratory tests revealed a hemoglobin level of 11.6 gm/dL, total leukocyte count of 5500 cells/mm³, and platelet count of 260,000/mm³. Serum electrolytes, renal function tests, and liver function tests were within normal limits. Tumor markers including lactate dehydrogenase (LDH), alpha-fetoprotein (AFP), and beta-human chorionic gonadotropin (beta-HCG) were within normal ranges. Contrast computed tomography (CT) of the chest demonstrated a lesion measuring 56 × 93 × 75 mm, involving both the anterior and middle mediastinum at the D2 to D5 level, with normal lung parenchyma present. The positron emission tomography-computed tomography (PET-CT) scan identified a conglomerated nodal mass measuring 6.8 × 9.9 cm, with necrosis in the anterior and middle mediastinum, encasing the mediastinal arteries, with a maximum standardized uptake value (SUV_max) of 17.3 and uninvolved lung parenchyma (Figure 1A and Figure 1B). A CT-guided biopsy was performed. The diagnosis was identified as spindle cell neoplasm. The tumor was histologically comprised of spindle cells (Figure 2A and Figure 2B). Multiple mitotic figures (exceeding four per ten high-power fields) were observed, along with localized regions of necrosis. Immunohistochemistry exhibited robust positivity for TLE-1 and Vimentin (Figure 3A and Figure 3B). STAT6, S100, DESMIN, PCK, CD23, MUC 4, and the major pulmonary tumor marker (TTF-1) yielded negative results (Figure 3C illustrates the negatives for PCK). SYT-SSX1/2 was positive, confirming the diagnosis of monophasic synovial sarcoma. Consequently, the integration of histological characteristics and immunohistochemical results led to a diagnosis of primary monophasic synovial sarcoma of the mediastinum. The patient was assessed for surgery and had a median sternotomy with tumor removal. The postoperative recuperation was uneventful. The patient underwent adjuvant treatment with ifosfamide and adriamycin. The patient is undergoing frequent follow-up with no indications of residual or recurrent disease.

The designation synovial sarcoma is a misnomer, as the tumor does not originate from the synovium; it only mimics synovial tissue under light microscopy. It seems to originate from multipotent stem cells that can differentiate into mesenchymal and/or epithelial structures and do not exhibit synovial differentiation [3],[4]. Fewer than 10–20% of synovial sarcomas occur in sites other than extremities [1],[5]. Soft tissue sarcomas, such as angiosarcoma, leiomyosarcoma (LMS), sarcomatoid mesothelioma, rhabdomyosarcoma (RMS), and synovial sarcoma, constitute fewer than 0.01% of all malignant thoracic neoplasms [6]. A major population-based study indicates that approximately 17% of new soft tissue sarcoma cases, encompassing various histologic subtypes, occur in thoracic regions such as the pleura, lungs, and mediastinum, with an estimated incidence of 6 per million individuals [7]. However, there is a lack of data that precisely documents the incidence of synovial sarcoma cases originating largely in the mediastinum. Synovial sarcomas are morphologically categorized into monophasic and biphasic subgroups. The biphasic type is characterized by the proliferation of bland spindle-shaped cells, accompanied by indications of epithelial development. Monophasic subtypes, conversely, may exhibit solely spindle cells or, on occasion, exclusively an epithelial component [8]. A poorly differentiated type of synovial sarcoma is also acknowledged. The differential diagnosis of primary synovial sarcoma in the mediastinum is intricate due to the presence of numerous primary and metastatic cancers in this location. Immunohistochemistry is quite beneficial. Immunostains are crucial and corroborative for diagnosing a suspected case of synovial sarcoma. The presence of epithelial markers in both the glandular and spindle cell components substantiates the diagnosis. Epithelial membrane antigen (EMA) is the most common positive marker among the epithelial markers [9]. Pan-cytokeratin and cytokeratins 7 and 19 may also exhibit positivity in epithelial-like component and the spindle cell component [10]. Furthermore, bcl-2 positivity may be observed in certain instances [11]. Precise staging of the disease is essential for effective patient management and necessitates the evaluation of the primary tumor and the assessment for metastatic disease. Magnetic resonance imaging (MRI) has traditionally been the imaging modality for evaluating soft tissue masses; however, soft tissue sarcomas have lately been acknowledged for their heightened 18F-FDG uptake in PET; its added value in assessing metabolic activity, identifying nodal involvement, and aiding in comprehensive staging, which was critical for guiding surgical and therapeutic decisions [12]. Complete surgical resection remains the cornerstone of treatment, with margin-negative excision being the most significant determinant of long-term survival in primary mediastinal synovial sarcomas [13]. Radiotherapy is advised in those with positive margins [14]. The optimal role for chemotherapy administration for this tumor remains inadequately characterized, with scant research available [15]. The combination of adriamycin and ifosfamide has been utilized as adjuvant therapy and for recurrences [15]. Historically, synovial sarcoma has been seen as having a dismal prognosis, with metastases occurring in 50% of cases. The lung is the predominant site for metastasis, succeeded by lymph nodes and bone. Nonetheless, not all synovial sarcomas have the same unfavorable prognosis any longer. Spillane et al. established that a diagnosis age above 20 years and a tumor size greater than 5 cm correlated with a markedly poorer prognosis [16],[17]. Nevertheless, the prognosis with intensive multimodal therapy is favorable, with confirmed survival extending up to 14 years [15].

The mediastinum is an atypical location for synovial sarcoma, as seen in the index case, often contributing to diagnostic uncertainty. This case underscores the need to include synovial sarcoma in the differential diagnosis of spindle cell and biphasic mediastinal tumors, and highlights the critical role of timely clinical suspicion, histopathology, and targeted immunohistochemistry in confirming this rare diagnosis. An aggressive multimodal treatment approach is recommended, as demonstrated by our patient’s favorable response to surgical resection followed by chemotherapy.